Hydrogen sulfide (H2S) is a recognized endogenous gasotransmitter involved in multiple signaling pathways that impact various aspects of physiological and pathological processes. Such processes include, but are not limited to; pain, inflammation, neurodegenerative disorders, regulation of breathing, respiratory disorders, cutaneous injuries, regulation of blood pressure, metabolic disorders, and urinary disorders, among others. Cystathionine-γ-lyase (CSE) is a key enzyme involved in the generation of H2S and an important target for therapeutic intervention in H2S-mediated pathologies and disorders. Compounds that can effectively modulate CSE activity will provide important therapeutic opportunities in disorders sensitive to H2S production.